Six single nucleotide polymorphisms (SNPs); rs4656461 (TMCO1), rs4619890 (AFAP1), rs11969985 (GMDS), rs4977756 (CDKN2B_AS1), rs2472493 (ABCA1) and rs10483727 (SIX1/SIX6); have recently been reported to be associated with the development of primary open angle glaucoma (OAG). We aimed to determine whether these risk alleles are independently associated with an increased risk of primary open angle glaucoma (POAG) in at least one eye in the Blue Mountains Eye Study (BMES) cohort, and evaluate genetic risk scores for POAG.

Methods

OAG diagnosis by expert panel was based on masked glaucomatous visual field loss and matching optic disc appearance, independent of intraocular pressure. Genetic analysis was performed using Illumina HumanHap670 quad arrays. Logistic regression models were used to assess associations between the genetic loci and POAG, adjusting for age and gender. Risk scores were constructed quantifying the effect of each additional risk allele among SNPs significant together in multivariable modeling.

These recently discovered SNPs were associated with OAG in a European-derived older population, each conferring about a 50% increased risk. Increasing number of risk alleles was associated with increasing glaucoma risk in a dose-dependent manner. Genetic risk scoring may have clinical utility by providing a glaucoma-enriched population for screening.